Transfer of a sample from a solid support into a liquid

ABSTRACT

An apparatus ( 10 ) and a method for concentrating and transferring volatile compounds contained in a sample on a detachable solid support ( 12 ) into a liquid for subsequent detection and/or analysis of the volatile compounds, are described. The apparatus comprises a holder ( 14 ) for the solid support ( 12 ), means ( 16 ) for transporting the holder ( 14 ) to a heating position on a heatable plate ( 18 ), a closed room-creating arrangement comprising the heatable plate ( 18 ) attached to a movable housing ( 30 ), the holder ( 14 ), the solid support ( 12 ), a funnel ( 20 ) on the solid support ( 12 ), and inside the funnel ( 20 ) a cold spot ( 22 ), means inside the housing ( 30 ) for heating the heatable plate ( 18 ) to evaporate the volatile compounds which then are condensed on the cold spot ( 22 ), means ( 24 ) for transporting the cold spot ( 22 ) from a cooler ( 26 ) to the inside of the funnel ( 20 ) and from there to a position ( 28 ) where condensed compounds are removed from the cold spot ( 22 ) into a liquid.

The present invention relates to transfer of a sample, or more preciselyvolatile compounds contained in the sample, from a solid support into aliquid. The invention is particularly concerned with a method andapparatus for transferring volatile compounds contained in a sampleplaced on a solid support into a liquid for detection and/or analysis ofone or several of the volatile compounds.

BACKGROUND

In the development of apparatuses and methods for detection and/oranalysis of volatile compounds contained in a sample or milieu,improvements of all components and steps are of interest.

In our PCT application WO 98/57141 is disclosed a system for thedetection of an analyte in air. The collected air sample is transportedto a first enrichment stage for enrichment of the analyte comprising athermally regulated adsorption/desorption filter creating a non-laminargas flow for adsorption of the analyte on the filter surfaces, encasedin a housing having a gas inlet and a gas outlet connected to valves.The desorbed analyte from the filter is transported to a secondenrichment stage, comprising a cold trap, for the further enrichment ofthe gaseous analyte by condensing the analyte, followed by extraction ofthe condensed material with a solvent, and collection of the solutionenriched in analyte from the cold trap for transport to an analysisunit.

By transporting the desorbed analyte out of the filter housing with aweak gas flow to a cold trap for condensing the analyte on its walls andthen rinsing the cold trap with a liquid to obtain a small liquidsample, some of the analyte is lost. It would be desirable to greatlyreduce or eliminate the loss of analyte, i.e. loss of condensed volatilecompounds, encountered in the prior art, particularly in cases wherevery small amounts of volatile compounds, in nanogram or picogramregion, are to be detected or analyzed.

DESCRIPTION OF THE INVENTION

The present invention provides an improved apparatus and a method forconcentrating and transferring volatile compounds contained in a solid,liquid or pre-concentrated gaseous sample placed on a detachable solidsupport into a liquid for subsequent delivery to an analysis unit fordetection and/or analysis of one or several of the volatile compounds.

Thus, the present invention provides a system or an apparatus forconcentrating and transferring volatile compounds contained in a solid,liquid or pre-concentrated gaseous sample placed on a detachable solidsupport into a liquid for subsequent delivery to an analysis unit fordetection and/or analysis of one or several of the volatile compounds.The system or apparatus comprises a holder for the solid support,transporting means for transporting the holder from a solidsupport-receiving position to a heating position and back, the heatingposition being on top of a heatable plate, a closed room-creatingarrangement comprising the heatable plate attached to a movable housing,the holder, the solid support, preferably a glass fiber based filter, afunnel on top of the solid support, and inside and on top of the funnela cold spot, thermally regulated heating means inside the housing forheating the heatable plate to a temperature evaporating the volatilecompounds which then are condensed on the cold spot, transporting meansfor transporting the cold spot from a cooler position to the inside andthe top of the funnel as part of the closed room-creating arrangementand from the closed room-creating arrangement to a position wherecondensed compounds are removed from the cold spot into a liquid, andback to the cooler position.

The invention further provides a method for concentrating andtransferring volatile compounds contained in a solid, liquid orpre-concentrated gaseous sample placed on a detachable solid support,preferably a glass fiber based filter, into a liquid for subsequentdelivery to an analysis unit for detection and/or analysis of one orseveral of the volatile compounds. The method comprises the steps ofpositioning the solid support on a holder, transporting the holder to aposition on top of a heatable plate, arranging a closed room comprisingthe holder, the heatable plate attached to a movable housing, the solidsupport, a funnel on top of the solid support, and inside and on top ofthe funnel a cold spot, heating the plate to evaporate the volatilecompounds from the sample on the solid support and to condense thevolatile compounds on the cold spot, and transporting the cold spotcarrying the condensed volatile compounds from the closed roomarrangement to a position where the condensed compounds are removed fromthe cold spot into a liquid.

The pre-concentration or transfer of a sample containing volatilecompounds from a solid, liquid or gaseous milieu, particularly from air,onto a solid support, for example a filter of some type that isnon-degradable at elevated temperatures, especially a glass fiber basedfilter, can be conducted in any suitable way. For example, thepre-concentration may be performed in some way known from the prior art,e.g. by vacuuming, by surface rubbing or by placing a sample onto thesolid support. It is an advantage to have a detachable solid support,e.g. a filter, which is cheap and readily disposable so that a newsample can be placed on a new solid support, thus eliminating anotherwise necessary cleaning procedure.

The subsequent detection and/or analysis of one or several of thevolatile compounds, originating from the sample and transferred into aliquid, can be performed in some way known from the prior art such aswith e.g. an immuno-sensor, UV-cell, Gas chromatograph (GC), liquidchromatography columns etc.

The present invention is particularly useful in cases where it isadvantageous, or even necessary, to concentrate a large sample of amilieu containing a small concentration of volatile compounds to bedetected and/or analyzed.

The purpose of the method and apparatus of the invention is thus toconcentrate preferably as much as possible, and transfer, volatilecompounds contained in a solid, liquid or pre-concentrated gaseoussample placed on a solid support into a liquid, preferably to as small avolume of liquid as possible, in order to improve the sensitivity of aselected detection and/or analysis process.

It should be understood that the term “pre-concentrated gaseous sample”is used to describe the liquid or solid particles that are trapped on asolid surface, preferably a filter, when the gaseous milieu is passed byor through the surface.

An important element of this invention is a heat desorption step, whichvaporizes the volatile compounds in the sample on the solid support. Thecreated vapor is subsequently condensed onto a cold surface, i.e. asolid cold spot. The condensed material on the cold spot is subsequentlyflushed or rinsed with a liquid from the cold spot to form a preferablysmall liquid sample or is directly dissolved in a preferably smallamount of solvent by immersion of the cold spot into a volume or streamof solvent, which then is transferred to a selected analysis unit.

The volatile compounds can be desorbed from a sample on the solidsupport into vapor form by either direct heating of a dry sample on thesolid support or by wetting the sample on the solid support with adesired amount of e.g. water and steam distilling the substances off thesolid support as a vapor mix. In both cases the vapor-phase is condensedon a cold spot.

The present invention is thus a link between pre-condensation orsampling of a desired milieu and an analysis unit used for detectionand/or analysis of one or several volatile compounds from a preferablysmall liquid sample. Examples of volatile compounds that may beconcentrated or purified and transferred from a sample on the solidsupport into a preferably small liquid sample with the apparatus andmethod of the present invention are low molecular weight substances,such as explosive substances (e.g. TNT, RDX), narcotics (e.g. cocaine,cannabis, heroine, amphetamines) and low-molecular weight biologicallyactive compounds or biologically degraded compounds.

The invention will now be illustrated by the following description ofembodiments, examples and the drawing, but it should be understood thatthe scope of protection is not limited to the disclosed details.

SHORT DESCRIPTION OF THE DRAWING

The drawing is a schematic side view of elements comprised by anembodiment of the apparatus according to the invention.

DESCRIPTION OF EMBODIMENTS

A sample containing volatile compounds on a solid support, e.g. obtainedfrom a pre-concentrator, is treated in the following way. Reference ismade to the elements shown in the drawing.

The solid support 12 is positioned on a holder 14 in a transferapparatus 10 of the invention. The shape and size of the holder 14 isadapted to receive the solid support 12. When the solid support is inplace on the holder 14, transporting means 16 for transporting orswinging the holder 14 from a solid support-receiving position to aheating position, the heating position being on top of a heatable plate18, which is a part of a closed room-creating arrangement forming adesorption unit and comprising the heatable plate 18 attached to amovable housing 30, the holder 14, the solid support 12, a funnel 20 ontop of the solid support 12, and inside and on top of the funnel 20 acold spot 22.

In the desorption unit there is thermally regulated heating means insidethe housing 30 for heating the heatable plate 18 to a temperatureevaporating desired volatile compounds, but preferably not decomposingthem. The vapors are condensed on the cold spot 22.

In a presently preferred embodiment, the metal plate is heated by alight source or an electrically heated foil inside the housing 30.Improved results are obtained when the solid support 12 is firmlyattached to the metal plate 14. This may be facilitated by the use of ametal net or the like between the solid support 12 and the funnel 20which then will be pressed against the outer edges of the solid support12. The funnel shaft 21 has a form and a size that is adapted to receivethe cold spot 22 at a short distance from the inner walls of the shaft.

The cold spot 22 is transported by the transporting means 24 from acooler 26 position to the inside and the top of the funnel 20 as part ofthe closed room-creating arrangement, i.e. the desorption unit

Thus, the cold spot 22 is cooled in a cooler 26 prior to being insertedinto the shaft 21 of the funnel 20 in such a way that a small, air-tightroom is formed between the shaft inner walls and the cold spot 22. Inthe drawing, the cold spot 22 is illustrated by a rod, or in fact tworods 22,22′ that can be used one after the other for transferring twosubsequent samples.

When the solid support 22 swings into the position on the metal plate ontop of the housing 30, the optional metal net, the funnel 20 and thecold spot 22 are rapidly brought into position to form the smallair-tight room, and the metal plate is either already heated prior toreceiving the solid support or is rapidly heated at this stage.

As the sample on the solid support 12 is heated, the volatile compoundsare evaporated and subsequently condensed on the cold spot 22. Improvedresults are obtained if the funnel 20 is kept warm.

Transporting means 24 then lifts the cold spot carrying the condensedmaterial up from the funnel shaft 21 and thus from the closedroom-creating arrangement, i.e. desorption unit, and swings it to aposition 28 where condensed compounds are removed from the cold spot 22into a liquid.

At the position 28 the condensed compounds are removed from the coldspot 22 by flushing or rinsing with a liquid to form a preferably smallliquid sample or are directly dissolved in a preferably minimal amountof solvent by immersion of the cold spot 22 into a volume of solvent orinto a stream of solvent forming a plug in the stream, which then istransferred to the selected analysis unit.

For a new cycle, the transporting means 16 for transporting or swingingthe holder 14 from a solid support-receiving position to a heatingposition, will transport the holder 14 back to the solidsupport-receiving position, and the transporting means 24 will transportthe cold spot 22, optionally after cleaning, to the cooler position 26.

In an embodiment of the invention the heat source is placed into avertically movable housing 30. The housing is e.g. cylindrical aroundthe heat source. Between the heated filter 12 and the funnel 20, insidethe funnel, there is a separate aluminum hood (not shown in the drawing)having a hole concentric with the funnel shaft 21 for receiving the tipof cold spot inside the closed room defined by the hood and the filter12. There may also be some insulating space between the hood and thelower portion of the funnel 20. Such an arrangement keeps most of theheat within the hood whilst preventing the outer surface of the funnel20 from becoming too warm.

When the solid support is in place over the heat source, the housing,the optional hood and the heat source are in one embodiment movedupwards. The solid support is thereby squeezed between the hood and afixed cone or dome or funnel 20 located over the solid support, thuscreating an inner seal close to the perimeter of the solid support. Thecontact surface of the solid support and the funnel is narrow and of thesame shape as the solid support. It is positioned to be a small distanceinside the outer edge of the solid support, maximizing the surfaceavailable on the solid support for desorption of the sample thereon. Inthis way there is a small, well defined volume created over the solidsupport.

The height of the cone or funnel should be such as to ensure that theappropriate volume is achieved. At this stage, a compatible liquid maybe introduced into the defined volume before the heat source isactivated or it may be left in a dry state. When the heat source isactivated and the temperature increases the substances on the solidsupport are transferred either by the rapid vaporization of the liquid(“Steam” extraction”) carrying the substances in the “steam” or bydirect dry state vaporization or sublimation of the substances into thevolume above the solid support and subsequently condensed on a coolsurface (cold spot).

The cool surface or cold spot can have many topologies but as an examplethe process will be described using a rod. The rod is inserted through ahole at the top of the funnel and is preferably positioned such that theend part of the rod is close to the surface of the solid support. Therod has been cooled to a temperature below room temperature before it isinserted into the funnel. It might be necessary to cool down the rodalso during the evaporation step to keep the rod temperature low enoughto maximize the amount of condensed material on the rod. The cooling canbe achieved a by a number of established techniques, such as by anactive heat exchanging construction or just by heat transport from thetip to a larger cool bulk of the rod material itself. However,preferably it should be ensured that the temperature is as low aspossible without condensing too much moisture from the surrounding air.The cold rod now acts as a condensation spot for the vaporizedsubstances emerging from the warm solid support. The vaporizedsubstances will condense on the first cold surface they meet, whichaccording to the design of this apparatus will be a defined area of therod. It is also important to keep the surrounding walls of the funnelwarmer than the cold rod to prevent vapor from condensing there insteadof on the rod.

In the disclosed embodiment of the apparatus of the invention, theheated vapors are deposited on the lowest part of the chilled area ofthe rod in near quantitative yields (see Table 1). Experiments haveshown that no additional gas flow is necessary during the vaporizationprocess, but the general construction of the apparatus and method of theinvention does not exclude the use of a gas flow. However, a gas flowmay decrease the yield of condensed material on the rod and is thereforenot preferred. A gas flow probably disturbs the diffusion gradient,which is directed towards the cold surface. The flow of gas from thevaporization process is normally of sufficient volume and pressure toensure rapid movement of the gases to the rod but under some conditionsit may be necessary to assist the flow. This assistance will be providednaturally by the rapid vaporization of the liquid on the solid support(if used) or by an auxiliary source or by forced extraction of the gasesfrom the cone, e.g. by vacuum.

In a presently preferred embodiment the top surface of the housing isflat or slightly convex to match the solid support and create as goodand firm contact with its base as possible. From experiments it isevident that favorable results are obtained when a firm contact betweenthe solid support and the hot surface is established. This is probablydue to the avoiding of reverse diffusion of the substances throughand/or behind the solid support. Heating the solid support directly bythe heat source without the flat top surface of the housing and the firmcontact between the heat source and solid support does not worksatisfactorily, probably due to back diffusion in the apparatus.

In one embodiment of the invention the heat source is being used as avery fast heater for rapidly heating up the filter material to about300° C. The heat transfer from the heat source to the solid support goesvia the top surface of the housing. The temperature on the cold side ofthe solid support should preferably be at least 240° C. to allow all thesubstances tested so far to vaporize and condensate (sublimate) onto thetip of the rod. However, the temperature may in some cases be lower.Heating time is also a parameter of great importance. Preferably thesolid support should not be heated more than for a maximum of 30 secondsin order not to degrade the substances, but also to keep the rod coldduring the process. Best results so far are obtained when the topsurface of the housing and the optional hood already has been pre-heatedto a temperature of around 300° C. prior the contact with the solidsupport. In this way the overall heating time is reduced by almost afactor two.

The condensed volatile compounds on the tip of the rod, i.e. cold spot,can be removed and taken into solution by immersing the active area ofthe rod in a small volume of an appropriate solvent, such as water. Thissolution containing the volatile compounds can then be transferred tothe analysis unit.

In an embodiment of the invention the rod can be moved to anotherposition where it is washed with a suitable solvent prior to a newcycle.

In an automated embodiment of the invention the rod is moved by a stepmotor into the small device containing a small amount of solvent (e.g.5-100 μl), such as water, after the sample has been deposited on the rodin the desorption part of the apparatus. The dimensions of this deviceshould be such that the solvent forms a thin film rinsing the lower partof the rod, which contains most of the condensed substances.

When the substances have been transferred from the rod to a liquid, e.g.dissolved in a solvent, the transfer of the liquid or solution may beaccomplished by opening a valve whereby the solution may e.g. enter intoa liquid stream as a liquid plug, e.g. in a loop, and the liquid plugcan be introduced into an analyzing unit e.g. an immuno-sensor, UV-cell,GC, liquid chromatography columns etc. The duration of the dissolutionstep typically does not take more than 5 seconds.

When the condensed volatile compounds have been dissolved from the rod,which, if necessary, is washed, the rod is returned to the coolerposition followed by the position above the solid support holder whichis in position for heating, and the process can be repeated. The rod canalso be washed with additional water or solvent and re-chilled by asuitable technology on its way back to the collecting spot for a newcycle.

A reversible heat exchanger can be used both for cooling down the rodbefore and during the desorption process and heating it in thedissolution process to shorten the total desorption and dissolutionprocesses. This could be advantageous in case the volatile compoundshave poor solubility in the preferred solvent.

In an embodiment, the diameter of a solid support in the form of a glassfiber based filter is in the order of 2 cm. The dimensions of the cooledsurface of the rod are a compromise between collecting as muchsubstances as possible from the solid support and using as little liquidas possible when washing off the condensate. By using a rod diameter ofabout 6 mm the substances on the tip can be dissolved in a liquid volumeof 50-100 microliters.

Another way of collecting the sample vapors in the desorption processfrom the solid support is to condense or dissolve the substances in amoving film of solvent. The solvent film moves over a collecting areapositioned directly above the heated solid support at a suitabledistance. The amount of water needed is about 25-100 μl in the abovedisclosed embodiment. The solvent film is very thin but of sufficientvolume to dissolve the amount of substance needed for a positiveidentification in the analysis unit.

Examples of Use of the Method and Apparatus of the Invention

Solid supports in the form of a glass fiber based filters of 2 cmdiameter are spiked with various amounts (about 1-100 ng) of substances.The solid supports are placed on the metal plate in an apparatus of theinvention, (c.f. the drawing) and the plate is heated to varioustemperatures during various desorption times (see Table 1). Thematerials on the rod are then dissolved using a small amount of water(50 microliters). The water is extracted with hexane and the hexanephase is analyzed by Gas Chromatography (GC). As can be seen in thetable, the results showed almost a quantitative recovery of thematerials on the solid supports. TABLE 1 Yield of various substances inthe small liquid samples after desorption from spiked solid supports.Desorption Desorption Desorption Time for water Yield water Substancetemp. time yield dissolution dissolution Pyrene 300° C. 15 sec. 100%  30sec. 50% Amphetamine 250° C. 10 sec. 85% 15 sec. 100%  Cocaine 300° C.15 sec. 85% 30 sec  85% Tetrahydrocannabinol 350° C. 30 sec. 75% 30 sec.75% (THC)

In summary, the present invention provides an apparatus for transferringan optionally pre-concentrated sample containing volatile compounds froma solid support into a liquid for delivery to an analysis unit fordetection and/or analysis of volatile compounds, comprising a holder forthe solid support, transporting means for transporting the holder from asolid support-receiving position to a heating position, the heatingposition being on top of a heatable plate, a closed room creatingarrangement comprising the heatable plate, the solid support, a funneland inside the funnel a cold spot, transporting means transporting thecold spot from the closed room to a position where condensed compoundsare removed from the cold spot into a liquid.

The invention further provides a method for transferring an optionallypre-concentrated sample containing volatile compounds from a solidsupport into a liquid for delivery to an analysis unit for detectionand/or analysis of volatile compounds, comprising the steps ofpositioning the solid support on a holder, transporting the holder to aposition on top of a heatable plate, arranging a closed room comprisingthe heatable plate, the solid support, a funnel and inside the funnel acold spot, heating the plate to evaporate the sample from the solidsupport and to condense the volatile compounds on the cold spot, andtransporting the cold spot from the closed room to a position wherecondensed compounds are removed from the cold spot into a liquid.

1. An apparatus (10) for concentrating and transferring volatilecompounds contained in a solid, liquid or pre-concentrated gaseoussample placed on a detachable solid support (12) into a liquid forsubsequent delivery to an analysis unit for detection and/or analysis ofone or several of the volatile compounds, which comprises a holder (14)for the solid support, transporting means (16) for transporting theholder (14) from a solid support-receiving position to a heatingposition and back, the heating position being on top of a heatable plate(18), a closed room-creating arrangement comprising the heatable plate(18) attached to a movable housing (30), the holder (14), the solidsupport (12), a funnel (20) on top of the solid support (12), and insideand on top of the funnel (20) a cold spot (22), thermally regulatedheating means inside the housing (30) for heating the heatable plate(18) to a temperature evaporating the volatile compounds which then arecondensed on the cold spot (22), transporting means (24) fortransporting the cold spot (22) from a cooler (26) position to theinside and the top of the funnel (20) as part of the closedroom-creating arrangement and from the closed room-creating arrangementto a position (28) where condensed compounds are removed from the coldspot (22) into a liquid, and back to the cooler (26) position.
 2. Theapparatus (10) according to claim 1, wherein the detachable solidsupport (12) is a glass fiber based filter.
 3. A method forconcentrating and transferring volatile compounds contained in a solid,liquid or pre-concentrated gaseous sample placed on a detachable solidsupport into a liquid for subsequent delivery to an analysis unit fordetection and/or analysis of one or several of the volatile compounds,which comprises the steps of positioning the solid support on a holder,transporting the holder to a position on top of a heatable plate,arranging a closed room comprising the holder, the heatable plateattached to a movable housing, the solid support, a funnel on top of thesolid support, and inside and on top of the funnel a cold spot, heatingthe plate to evaporate the volatile compounds from the sample on thesolid support and to condense the volatile compounds on the cold spot,and transporting the cold spot carrying the condensed volatile compoundsfrom the closed room arrangement to a position where the condensedcompounds are removed from the cold spot into a liquid.
 4. The methodaccording to claim 3, wherein the detachable solid support is a glassfiber based filter.